Histamine Released From Skin-Infiltrating Basophils but Not Mast Cells Is Crucial for Acquired Tick Resistance in Mice.

Yuya Tabakawa,Kenji Ishiwata,Yohei Kawano,Naohiro Watanabe,Takahiro Adachi,Soichiro Yoshikawa,Kensuke Miyake,Hirotaka Kanuka,Hiroshi Ohtsu,Kayoko Yamaji,Elisabeth J Robinson,Yoshinori Yamanishi,Hajime Karasuyama,Takuya Ohta

doi:10.3389/fimmu.2018.01540

Abstract

Ticks are blood-feeding arthropods that can transmit pathogens to humans and animals, leading to serious infectious diseases such as Lyme disease. After single or multiple tick infestation, some animal species develop resistance to tick feeding, leading to reduced risk of pathogen transmission. In mice infested with larval Haemaphysalis longicornis ticks, both mast cells and basophils reportedly play key roles in the manifestation of acquired tick resistance (ATR), but it remains ill-defined how they contribute to it. Here, we investigated their products responsible for ATR. Treatment of mice with antihistamine abolished the ATR while histamine or histamine H1 receptor agonist reduced tick-feeding even in the first infestation. In accordance with these, mice deficient for histamine production showed little or no ATR, indicating the crucial role for histamine in the expression of ATR. Adoptive transfer of mast cells and basophils derived from histamine-sufficient or deficient mice to recipient mice lacking mast cells and basophils, respectively, revealed that histamine produced by basophils but not mast cells is essential for the manifestation of ATR, in contrast to the case of local and systemic anaphylaxis where mast cell-derived histamine is the major player. During the second but not first tick infestation, basophils accumulated and made a cluster, surrounding a tick mouthpart, in the epidermis whereas mast cells were scattered and localized mainly in the dermis, more distantly from a tick mouthpart. This appears to explain why basophil-derived histamine is much more effective than mast cell-derived one. Histamine-sufficient, but not -deficient mice showed the thickened epidermis at the second tick-feeding site. Taken together, histamine released from skin-infiltrating basophils rather than skin-resident mast cells plays a crucial role in the manifestation of ATR, perhaps through promotion of epidermal hyperplasia that may inhibit tick feeding.

Highlights

Ticks are blood-feeding ectoparasites of medical and veterinary public health importance [1]
Previous studies in cattle and guinea pigs suggested the contribution of histamine to Acquired tick resistance (ATR) [13, 15], but it remains to be determined whether this can be applied to other animal species such as mice
Considering the fact that the tick resistance is reportedly correlated with the amounts of histamine at the tick feeding site in cattle and guinea pigs [12, 15], it was hypothesized that histamine released from mast cells stimulated with immunoglobulin E (IgE) and tick antigens contributes to ATR in mice

Summary

Introduction

Ticks are blood-feeding ectoparasites of medical and veterinary public health importance [1] They are second to mosquitos as vectors of pathogens that cause infectious diseases, including Lyme disease, in humans [2, 3]. Ticks insert their mouthparts through the host skin to feed blood meal, and hard ticks (Ixodidae), in particular, require several days to weeks to replete with blood meal and drop off from the host [3]. We confirmed the essential role of mast cells in ATR in the case of C57BL/6 mice infested with Haemaphysalis longicornis (H. longicornis) ticks [9] Both basophils and mast cells contribute to the manifestation of ATR in this setting while the contribution of mast cells in guinea pigs remains to be determined

Methods

Results

Conclusion